Aldose reductase inhibitory evaluation and in silico studies of bioactive secondary metabolites isolated from Fernandoa. adenophylla (Wall. ex G. Don)

Diabetes and its associated secondary complications represent significant global health challenges. This study aimed to address these issues by investigating Fernandoa adenophylla, a plant utilized in various alternative medicine systems for its antidiabetic properties. Five compounds Lapachol (1), Alpha-lapachone (2), Peshawaraquinone (3), Dehydro-α-lapachone (4), and Indanone derivatives (5) were isolated from this plant and evaluated for their aldose reductase inhibitory potential. Among the compounds tested, Alpha-lapachone exhibited the highest efficacy with an inhibition rate of 86.4 % and an IC₅₀ value of 1.4 ± 0.5 μM, followed by Peshawaraquinone and Lapachol, which demonstrated inhibition rates of 82.9 % and 81.6 %, respectively. Further evaluations of these compounds included pharmacokinetic characterization and toxicity profiling using SwissADME, StopTox, Molinspiration, and ProTox 3.0 tools. Molecular docking studies were conducted to assess the interactions between the bioactive metabolites of F. adenophylla and aldose reductase. Most of the isolates exhibited notable antidiabetic properties, with the phytochemicals showing promising pharmacological attributes and demonstrating strong binding affinity and interactions within the allosteric site of the target protein (PDB ID: 3V36). Among the compounds investigated, Alpha-lapachone (2) emerged as the most promising candidate for drug development, pending further in vivo and clinical trials. These findings underscore the potential of F. adenophylla for clinical applications in managing diabetes and warrant further research to explore its therapeutic possibilities.